B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance

Abstract

The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment.

Overexpression of B7-H3 correlates with aggressive clinicopathological characteristics in non-small cell lung cancer

“…Wang et al [32] disclosed that high B7-H3 expression was an indicator of advanced stage and common pulmonary metastasis in osteosarcoma. In the current meta-analysis, we found that B7-H3 overexpression was correlated with lymph node metastasis, and advanced TNM stage, which were in accordance with previous findings [10, 14, 31, 32]. Notably, some studies [12, 32] showed that patients with high tumor B7-H3 levels had shorter survival time and recurrence time.…”

“…Qin et al [14] showed that B7-H3 expression was associated with multiple adverse clinical and pathologic features in renal cell carcinoma. Moreover, Huang et al [31] revealed that B7-H3 levels were significantly associated with tumor size in patients with cervical cancer. Wang et al [32] disclosed that high B7-H3 expression was an indicator of advanced stage and common pulmonary metastasis in osteosarcoma.…”

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

“…Overexpression of B7-H3 has been associated with multiple cancers including esophageal cancer [41], pancreatic cancer [26], cervical cancer [36], non-small-cell lung cancer [38] and colorectal cancer [37]. However, high B7-H3 expression is also reported to be associated with better survival in acute myeloid leukemia [23].…”

The third group of the B7‐CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7‐H3

“…Its expression was also associated with disease progression or advanced stage in pancreatic cancer, prostate cancer, breast cancer, melanoma, clear cell renal cell carcinoma (RCC), oral squamous cell carcinoma, and non‐small cell lung cancer (NSCLC) . Similarly, studies have also found a direct correlation with increased B7‐H3 expression and tumor size, tumor grade, and rate of recurrence in humans . Thus, there is ample evidence for the association of B7‐H3 with poor prognosis in human cancers.…”